First evidence of industrial fly-ash in an Antarctic ice core.

Spheroidal carbonaceous particles (SCPs) are a component of fly-ash, the particulate by-product of industrial high temperature combustion of fuel-oil and coal-series fuels. We provide the first evidence that these indelible markers of industrialisation have been deposited in Antarctic ice, thousands of kilometres from any potential source. The earliest observed particle was deposited in an ice layer from 1936 CE. While depositional fluxes are low, chemical analysis of individual SCPs indicates a coal combustion origin.

Neuroprotective effects of notoginsenoside R1 by upregulating Trx-1 on acrylamide-induced neurotoxicity in PC12.

Acrylamide (ACR) is a water-soluble chemical that is commonly used in chemical and cosmetic manufacture. Many studies have been carried out to investigate the neurotoxicity mechanisms of ACR, resulting in oxidative stress and nerve damages. One of the commonly used traditional Chinese medicines is notoginsenoside R1 (NR1). However, its mitochondrial-mediated apoptotic effect caused in ACR-induced neurotoxicity has not been reported. Our results have shown that NR1 resisted the neurotoxicity induced by ACR by upregulating the levels of thioredoxin-1 (Trx-1) in Rat adrenal chromaffin cell tumor (PC12) cells. NR1 inhibited the increase in levels of Bax, caspase-9, and caspase-3, which was instigated by ACR. Moreover, NR1 inhibited the decrease in levels of B-cell lymphoma 2 and Trx-1 induced by ACR. The downregulation of Trx-1 aggravated the mitochondrial-mediated apoptosis and increased the expression of the above molecules, which was induced by ACR. In contrast, overexpression of Trx-1 attenuated the mitochondrial-mediated apoptosis and inhibited the expression of the mentioned molecules induced by ACR. Our results suggested that NR1 protected ACR-induced mitochondrial apoptosis by upregulating Trx-1.

Organic Compounds in a Sub-Antarctic Ice Core: A Potential Suite of Sea Ice Markers.

Investigation of organic compounds in ice cores can potentially unlock a wealth of new information in these climate archives. We present results from the first ever ice core drilled on sub-Antarctic island Bouvet, representing a climatologically important but understudied region. We analyze a suite of novel and more familiar organic compounds in the ice core, alongside commonly measured ions. Methanesulfonic acid shows a significant, positive correlation to winter sea ice concentration, as does a fatty acid compound, oleic acid. Both may be sourced from spring phytoplankton blooms, which are larger following greater sea ice extent in the preceding winter. Oxalate, formate, and acetate are positively correlated to sea ice concentration in summer, but sources of these require further investigation. This study demonstrates the potential application of organic compounds from the marine biosphere in generating multiproxy sea ice records, which is critical in improving our understanding of past sea ice changes.

Integrating medication samples into the traditional community pharmacy supply chain: a feasibility study.

OBJECTIVE: To assess the feasibility of a medication sampling program involving community pharmacists. METHODS: A community pharmacy dispensed samples after receiving a voucher given to patients by prescribers. Surveys explored prescribers' and patients' views about sampling and patients' experiences with the program. KEY FINDINGS: Half of prescribers reported providing samples, yet 15 patients redeemed 18 vouchers over 1 year. Patients expressed favourable views towards sampling and pharmacist involvement, despite more than half (n = 8/15, 53%) feeling that visiting the pharmacy was less convenient. CONCLUSION: A voucher-based medication sampling program based in a community pharmacy is a model integrating pharmacist care.

Sea salt sodium record from Talos Dome (East Antarctica) as a potential proxy of the Antarctic past sea ice extent.

Antarctic sea ice has shown an increasing trend in recent decades, but with strong regional differences from one sector to another of the Southern Ocean. The Ross Sea and the Indian sectors have seen an increase in sea ice during the satellite era (1979 onwards). Here we present a record of ssNa+ flux in the Talos Dome region during a 25-year period spanning from 1979 to 2003, showing that this marker could be used as a potential proxy for reconstructing the sea ice extent in the Ross Sea and Western Pacific Ocean at least for recent decades. After finding a positive relationship between the maxima in sea ice extent for a 25-year period, we used this relationship in the TALDICE record in order to reconstruct the sea ice conditions over the 20th century. Our tentative reconstruction highlighted a decline in the sea ice extent (SIE) starting in the 1950s and pointed out a higher variability of SIE starting from the 1960s and that the largest sea ice extents of the last century occurred during the 1990s.

Medication reconciliation interventions in ambulatory care: A scoping review.

PURPOSE: The published literature on medication reconciliation (MR) interventions, outcomes, and facilitators in ambulatory care settings is reviewed. METHODS: A scoping review was conducted to characterize ambulatory care-based MR research in terms of study design, elements of interventions, and outcomes examined. English-language articles on comparative studies of MR programs targeting adults in ambulatory care settings were identified using data sources including MEDLINE, PreMEDLINE, EMBASE, and International Pharmaceutical Abstracts. For each study, steps undertaken in the MR process were extracted. The Cochrane Effective Practice and Organisation of Care (EPOC) taxonomy was used to classify types of interventions; taxonomies for reported outcomes and factors facilitating implementation of MR initiatives were developed by the authors. RESULTS: From among 2062 publications screened, 15 were included in the review. In 13 studies, multiple data sources were used to compile a "best possible medication history" (BPMH); however, the BPMH was shared with external healthcare providers in only 4 studies and with patients in only 5 studies. Most reported MR interventions were classified into two EPOC domains: professional (predominantly educational outreach visits and patient reminders) and organizational (predominantly provider-oriented interventions). Process outcomes were reported in 12 studies, with correct performance of MR being the most commonly evaluated process outcome, and 9 studies identified factors that facilitated MR implementation. CONCLUSION: Few studies have examined clinical outcomes of MR in ambulatory care settings, with the majority of pertinent reports focusing instead on process outcomes. Facilitators of successful MR interventions have been identified at the patient, staff, and clinic setting levels.

Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder.

Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.

Antarctic-wide array of high-resolution ice core records reveals pervasive lead pollution began in 1889 and persists today.

Interior Antarctica is among the most remote places on Earth and was thought to be beyond the reach of human impacts when Amundsen and Scott raced to the South Pole in 1911. Here we show detailed measurements from an extensive array of 16 ice cores quantifying substantial toxic heavy metal lead pollution at South Pole and throughout Antarctica by 1889 - beating polar explorers by more than 22 years. Unlike the Arctic where lead pollution peaked in the 1970s, lead pollution in Antarctica was as high in the early 20(th) century as at any time since industrialization. The similar timing and magnitude of changes in lead deposition across Antarctica, as well as the characteristic isotopic signature of Broken Hill lead found throughout the continent, suggest that this single emission source in southern Australia was responsible for the introduction of lead pollution into Antarctica at the end of the 19(th) century and remains a significant source today. An estimated 660 t of industrial lead have been deposited over Antarctica during the past 130 years as a result of mid-latitude industrial emissions, with regional-to-global scale circulation likely modulating aerosol concentrations. Despite abatement efforts, significant lead pollution in Antarctica persists into the 21(st) century.

Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid nephropathy.

Experimental aristolochic acid nephropathy is characterized by early tubulointerstitial injury followed by fibrosis, reproducing chronic lesions seen in humans. In vitro, probenecid inhibits aristolochic acid entry through organic anion transporters, reduces specific aristolochic acid-DNA adduct formation, and preserves cellular viability. To test this in vivo, we used a mouse model of aristolochic acid nephropathy displaying severe tubulointerstitial injuries consisting of proximal tubular epithelial cell necrosis associated to transient acute kidney injury followed by mononuclear cell infiltration, tubular atrophy, and interstitial fibrosis. Treatment with probenecid prevented increased plasma creatinine and tubulointerstitial injuries, and reduced both the extent and the severity of ultrastructural lesions induced by aristolochic acid, such as the loss of brush border, mitochondrial edema, and the disappearance of mitochondrial crests. Further, the number of proliferating cell nuclear antigen-positive cells and total aristolochic acid-DNA adducts were significantly reduced in mice receiving aristolochic acid plus probenecid compared with mice treated with aristolochic acid alone. Thus, we establish the nephroprotective effect of probenecid, an inhibitor of organic acid transporters, in vivo toward acute proximal tubular epithelial cell toxicity in a mouse model of aristolochic acid nephropathy.

Surveillance and treatment of malignancy in Bloom syndrome.

We report a patient with Bloom syndrome, a rare autosomal recessive condition characterised by chromosomal instability leading to a high risk of cancer at an early age. The diagnosis should be considered in patients with any cancer of significantly early onset, short stature and a photosensitive lupus-like rash on the face. Diagnostic confirmation is obtained from chromosome studies that show significantly increased numbers of sister chromatid exchanges. There are important management implications, including minimising the use of ionising radiation in surveillance and treatment.

Availability of emergency contraception after its deregulation from prescription-only status: a survey of Ontario pharmacies.

In 2005 the emergency contraception formulation of levonorgestrel (Plan B) became available in Ontario pharmacies without a prescription. We surveyed 239 pharmacies 1 month before the regulatory change and 14-17 months after the change to determine whether availability of the drug increased. The response rates were 79% and 70% before and after the change in status. The proportion of pharmacies that had an in-stock supply of Plan B increased from 78% to 92% (p < 0.001). After the regulatory change, 87% of the surveyed pharmacies (95% confidence interval 82%-92%) reported that they had the drug in stock and were willing to dispense it behind the counter. Availability was similar for urban and rural pharmacies, but rural pharmacies had more restricted hours (e.g., 15% closed on weekends). Thus, as a result of the regulatory change, emergency contraception is more widely available, but access in rural areas is still limited by restricted pharmacy hours.

Availability of hormone replacement therapy products in Canada.

OBJECTIVES: To determine the availability in Canada of different types of hormone replacement therapy (HRT) products, and to compare the availability of HRT products in Canada to their availability in other countries. METHODS: A systematic review was conducted of the availability of products indicated for treatment of menopausal symptoms in Canada, the United States (US), the United Kingdom (UK), Sweden, and Australia. Products indicated for the treatment of menopausal symptoms were determined for each country by using on-line drug product databases. Products administered by injection and androgen products, unless combined with estrogens, were excluded from the analysis. RESULTS: There were 111 different brands identified in the 5 countries examined, with Canada having the lowest number of brands and active ingredients (28 and 22, respectively) compared to the other countries (Sweden and UK at 67 and 47 brands and 39 and 40 active ingredients, respectively). Not available in Canada are 34 active ingredients (either alone or in combination products) and 5 different types of formulations of HRT. There was a significant difference between the number of combination brand products available in Canada and in the UK (5 versus 29, P <.001, respectively). CONCLUSIONS: Canadian women have comparatively few options available to them for the management of menopausal symptoms. The wide range of HRT products available in other developed countries provides alternatives for managing side

Pharmacy provision of emergency contraception: the Ontario emergency contraception pilot project.

OBJECTIVES: To develop and evaluate a program to provide emergency contraception (EC) directly in pharmacies that would recruit and train pharmacists and physician partners, and inform women about the availability of EC in pharmacies. METHODS: Pharmacists and physicians working in the Scarborough, Rexdale, and North York regions of Toronto were recruited to receive a training program on EC. The pharmacists in each pharmacy were linked with a designated physician who retrospectively authorized prescriptions provided under the protocol. Client eligibility for EC was determined using a self-administered questionnaire that was reviewed by the pharmacist. A poster and radio campaign advertised the service, and a telephone hotline informed users of their nearest participating pharmacy. Data on the client's age, reasons for requesting EC, time elapsed from intercourse until presentation, and requests for follow-up referral were analyzed using descriptive methodology. User satisfaction was determined through a mail-back questionnaire. RESULTS: A total of 146 pharmacists practising in 40 pharmacies were linked with 34 physicians. In the 1 year of the project, 6931 prescriptions for EC were provided. Fifty-four percent of the women accessed EC within 24 hours of intercourse. The majority of women were very satisfied with the service, and 21.1% indicated that had they not obtained EC in this way, they would not have obtained it elsewhere. More information about birth control was desired by 10.2% of the women. CONCLUSION: Direct pharmacist provision of EC is an effective pregnancy-prevention strategy that is well accepted by the women who access it.

Emergency contraception: models to increase accessibility.

Much of the recent focus on emergency contraception (EC) has been on the need to increase the availability of EC without a prescription. Barriers to the wider accessibility of EC include the need to use the medication within a 72-hour window, cost, and knowledge about its availability. Concerns about the non-prescription accessibility of EC include missing the opportunity to see a physician, possible reduced use of barrier contraceptives and the resulting increase in sexually transmitted infections, and overuse of EC and underuse of regular contraception. As the wider availability of EC is a reality, and pressure to further increase its access is growing, it is timely that issues surrounding accessibility of EC be discussed. This paper explores the issues around making EC more accessible and the various models of obtaining EC, namely, prescription medication, pharmacist-physician collaboration, pharmacist-dispensed medication, schedule II (behind the counter) medication, or on-the-shelf medication. The ideal model will be the one that provides improved accessibility for adolescents, other low-income women, and indeed for all women. Increased accessibility of EC should also lead to cost savings for the health-care system because of fewer unwanted pregnancies.

Th1 and Th2 CD4+ T cells provide help for B cell clonal expansion and antibody synthesis in a similar manner in vivo.

The relative ability of Th1 and Th2 T cells to help B cells remains controversial as do the mechanisms by which both T cell subsets provide help in vivo. Whether this help affects the clonal expansion and/or differentiation of B cells has been difficult to assess due to the low frequency of Ag-specific T and B lymphocytes. We have employed a novel technique to directly monitor the clonal expansion of Ag-specific T and B lymphocytes in vivo. OVA-specific TCR transgenic T lymphocytes were polarized toward a Th1 or Th2 phenotype in vitro. These cells were then transferred into syngeneic recipients, along with B cell receptor transgenic hen egg lysozyme-specific B lymphocytes. Our results indicate that Th1 and Th2 cells support B cell responses to a similar extent in vivo and that they achieve this in the same manner by migrating into B cell follicles to promote CD154-dependent B cell clonal expansion and Ab production.

Inadequate history as a barrier to immunization.

OBJECTIVES: To evaluate how lack of immunization history contributes to missed opportunities for immunization and to document the effort required to obtain immunization history. DESIGN: Cross-sectional. SETTING: Urban, inner-city primary care pediatric clinic serving a low-income, multiethnic population. PATIENTS: Ninety-five new patients seen for either well-child care (53 patients) or acute illnesses (42 patients) during a 4-month period in 1993. Fifty-nine patients were aged 3 to 59 months and 36 were aged 5 to 15 years. MEASUREMENTS: Efforts to obtain immunization history were documented by means of a standardized data collection form. RESULTS: Immunization history was obtained for only 26 (27%) of 95 patients during the initial visit. Caregivers of 74 (78%) of 95 patients did not bring immunization records to the initial visit; they were no more likely to bring records for well-child care than for acute care or for younger vs older children. Parents brought immunization records more often than did nonparents. A total of 145 telephone calls were made and 30 letters were sent in an attempt to obtain immunization histories. Immunization records were never found for 10 new patients (11%). Thirty-two patients (34%) were found to be lacking immunizations. Of these, only three patients had contraindications to immunization at the initial visit. Therefore, in one third of our new patients, opportunities to immunize were missed solely because their immunization records were unavailable at the initial visit. In another one third of cases, caregivers had incorrectly believed their child's immunizations to be up to date. CONCLUSIONS: Opportunities to immunize children were often missed because of a lack of immunization history. Our experience supports the need for improved documentation of immunization histories.

The cold chain and the expanded program on immunization in Chile: an evaluation exercise.

PIP: It was decided that a study of the cold chain should be conducted in Chile in an effort to identify situations that could be corrected and to improve the technical and administrative development of the program. Specifically, study objectives were as follows: to determine the degree to which the EPI standards for procurement, receipt, transfer, control, maintenance, and distribution of vaccines were being met; to assess the turnover, knowledge, and training of auxiliary vaccination personnel against the relevant standards established for vaccine and cold chain management; to determine the antigenic potency of measles vaccine samples available at the time visits were made to local clinics, regional health storage sites, and the central supply facility; and to test a written instrument designed for the express purpose of assessing achievement of the first 2 objectives cited. The study sought to provide a descriptive assessment of work being performed at the central, regional, and local levels in the Metropolitan Region. The operating units involved included the airport and main supply center at the central level; the 7 storage facilities of the Metropolitan Region's 78 local clinics providing maternal and child health care. 40 clinics, selected by lot, represented 51% of the region's 78 clinics and provided coverage for 49% of the population assigned to the region's health services. The units studied failed to satisfy half the investigated Expanded Program for Immunization (EPI) standards, i.e., the average achievement rating of the 3 levels combined (49.3%) fell short of half the desired 100%. The airport unit met very few of the EPI implementation standards, scoring only 20% in this area. Deficiencies were found in systems for shipping vaccine in cold boxes, for making cold rooms permanently available, and for providing adequate vaccine transportation. The central supply facility, responsible for the purchase, storage, distribution, and maintenance of an adequate vaccine stock, had an achievement score of only 41%. The regional level, represented by the 7 storage facilities studied, obtained a lower overall achievement score than the other 2 levels and appears to be a high-risk link in the cold chain. The local level, represented by the 40 clinics studied, attained the highest average achievement score of any level (57%). Yet, serious deficiencies also emerged at this level, particularly regarding implementation and control activities. These deficiencies were aggravated by the fact that vaccines undoubtedly encounter a larger number of potentially damaging contingencies at the local level than they do elsewhere. Suggestions are made for overcoming these difficulties.^ieng